Reduced cerebellar diameter in very preterm infants with abnormal general movements

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Abstract

Background

Abnormal General Movements (GMs) early in life are predictive of later neuromotor deficits and are related to white matter abnormalities on magnetic resonance imaging (MRI). However, other structural correlates of abnormal GMs have not been defined.

Aims

The objective of this study was to explore brain-metrics (linear brain measurements on MRI representative of 3-D brain volumes) at term as a predictor of abnormal GMs at 1 and 3 months' corrected age in preterm infants. It was hypothesized that abnormal GMs would be related to reduced brain-metrics in primary motor areas, namely the cerebellum and parietal lobes.

Study design

Eighty three preterm infants (< 30 weeks' gestational age) were scanned at term-equivalent age. MRI was assessed for white matter abnormality and brain-metrics in six predefined brain regions (i.e. bifrontal, biparietal, lateral ventricles and transverse cerebellar diameters, and inter-hemispheric distance).

Outcome measures

At 1 and 3 months' corrected age infants' GMs were assessed from video-taped footage and rated as normal or abnormal using standardized methodology.

Results

At 1 month, 63% (n = 52) of infants had abnormal GMs with no association between any of the brain-metrics and abnormal GMs. At 3 months, 23% (n = 18) of infants had abnormal GMs (absent fidgety movements n = 18; abnormal fidgety movements n = 0). Reduced bifrontal, biparietal, and cerebellar transverse diameters, along with an increase in lateral ventricle sizes were associated with an increased risk of abnormal GMs at 3 months' corrected age. After controlling for white matter abnormality and grade III/IV intraventricular haemorrhage, only the cerebellar transverse diameter was predictive of abnormal GMs at 3 months.

Conclusions

Reduced cerebellar diameter at term equivalent age is related to abnormal GMs at 3 months' corrected age, independent of white matter abnormality and intraventricular haemorrhage.

Introduction

With growing numbers of very preterm infants surviving due to advances in both obstetric and neonatal care, there are increasing numbers of children born very preterm with motor impairments [1]. Detecting which children will have later motor problems is challenging, however, Prechtl's method of assessing spontaneous movements in infants, also known as General Movement (GM) assessments has improved our understanding of early motor development [2]. In particular it has been shown that the quality of GMs within the first months of life are predictive of later motor problems, including early motor delay, minimal motor problems and cerebral palsy in very preterm children [3], [4], [5], [6].

In utero studies of fetal motility have demonstrated that GMs emerge around 9 weeks' gestational age and are thought to reflect the onset of supraspinal modulation of spinal and brainstem activity [7], [8]. Normal GM flow on to two distinct patterns, “writhing” GMs which are seen from term age up to 9 weeks and “fidgety” GMs which can appear as early as 6 weeks, but usually around 9 weeks, and are present until 20 weeks [2]. At approximately 4–5 months post term GMs disappear with the onset of goal directed voluntary movement. The disappearance of fidgety GMs is thought to be related to changes in the development of the cortical subplate [9]. The predictive value of GMs in identifying ongoing motor impairments is dependent on the type of GM pattern observed, with the fidgety movements being more strongly related to later neurological outcome than writhing movements [5], [10].

With advanced neuroimaging modalities like magnetic resonance imaging (MRI), there has been an improved understanding of the patterns of brain injury that relate to motor impairments seen in extremely preterm children [11], [12]. Periventricular white matter lesions, and cortical and deep grey matter lesions have also been related to motor impairments and some of these findings are evident on MRI as early as term corrected age [12], [13], [14]. Furthermore, these qualitative MRI abnormalities of white and grey matter are associated with reduction in volumes in specific regions including the thalamus, cortical grey matter, hippocampus and cerebellum [15], [16], [17]. However, the association between these specific volumetric abnormalities at term corrected age and functional neurobehavioural impairments, such as motor deficits is still not well understood. Thus, the association between brain size and functional motor correlates seen in early life requires further study.

Several studies have demonstrated that GMs are related to cerebral injury, however, it is unclear whether alterations in regional cerebral development are related to these abnormal movements [18], [19], [20]. Brain-metrics is a new technique that has been shown to be valid for quantifying brain growth and assessing brain atrophy using MRI in very preterm infants [21]. The advantage of brain-metrics is that it is a quick, simple and reliable technique that can be used by clinicians and researchers to measure brain growth and has been shown to correlate with brain tissue and fluid volumes [21].

The objective of this study was to explore a set of diameters of different brain regions (brain-metrics) as predictors of abnormal GMs at 1 and 3 months' corrected age in preterm infants. It was hypothesized that abnormal GMs would be related to the brain-metric measurements of the primary motor areas, namely the transverse diameter of the cerebellum and biparietal lobe. Since GMs reflect the integrity of the central nervous system, we hypothesized that other areas of the brain such as the frontal lobe may also be related to GMs [2]. Given that brain volumes and later outcome may be mediated by cerebral injury [15] it is important to establish whether the relationship between abnormal GMs and areas of brain growth or atrophy are independent of white matter abnormality and intraventricular haemorrhage IVH. The secondary hypothesis was that these relationships would be independent of white matter abnormality and grade III/IV IVH.

Section snippets

Subjects

This study included infants born very preterm (less than 30 weeks' gestation) at the Royal Women's Hospital, Melbourne, Australia between January 2005 and September 2006. This study was part of a larger randomized controlled trial of a preventative care program for very preterm infants that was not related to GM outcome. The intervention commenced post MRI and there was no difference in GMs at 1 and 3 months' corrected age between treatment and control groups. As this study involved home based

Statistical analysis

Data analysis was performed using Stata 10.0. Mean (standard deviation) brain-metric measurements are presented separately for infants with normal and abnormal GMs at 1 and 3 months. Odds ratios and 95% CI for abnormal GMs at 1 and 3 months' corrected age were calculated using separate multivariable logistic regression for each brain-metric measurement adjusted for the gestational age at the time of MRI, and gender. The relationship between each brain-metric and GMs was also adjusted for white

Results

Of the first 99 children recruited for the larger randomized controlled trial, 96 infants' had GMs assessed at both 1 and 3 months. Of these 96 infants, 84 infants' families consented to MRI. One infant's MRI data were excluded from the analysis due to insufficient quality to measure brain-metrics, resulting in complete MRI and GM data for 83 very preterm children. Of note, the infants were at high risk of adverse developmental outcomes in view of their low mean gestational age of 27 weeks and

Discussion

Understanding the neurobiological basis for abnormal GMs is important as it will assist in understanding the contribution of the differing forms of cerebral injury and/or cerebral development in early motor abilities. We have previously shown that white matter abnormality, IVH and PVL are related to abnormal GMs at 1 and 3 months' corrected age [18]. However, we did not find a significant relationship with any other perinatal variables including gestational age, birth weight, postnatal steroids

Acknowledgements

We would like to thank Jane Orton, Nisha Brown and the VIBeS Plus team, Murdoch Children's Research Institute for their assistance in collecting data. We acknowledge support from the National Health Medical Council (Australia) Public Health Postgraduate Scholarship for AS (Grant ID: 334390), NHMRC Career Development Award for RB and NHMRC Project grant (ID 284512), Murdoch Children's Research Institute, Myer Foundation, Allens Arthur Robinson, Cerebral Palsy Institute, Australia, and Thyne Reid

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  • Cited by (0)

    The study was approved by the Research and Ethics Committees at the Royal Children's Hospital and the Royal Women's Hospital. Infants were enrolled at 38–40 weeks' postmenstrual age, once informed parental consent was obtained.

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